3-132447465-G-A

Position:

chr3-132447465-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The ENST00000260818.11(DNAJC13):c.289G>A(p.Ala97Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000758 in 1,569,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

DNAJC13
ENST00000260818.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.59

Variant links:

Genes affected

DNAJC13 (HGNC:30343): (DnaJ heat shock protein family (Hsp40) member C13) This gene encodes a member of the Dnaj protein family whose members act as co-chaperones of a partner heat-shock protein by binding to the latter and stimulating ATP hydrolysis. The encoded protein associates with the heat-shock protein Hsc70 and plays a role in clathrin-mediated endocytosis. It may also be involved in post-endocytic transport mechanisms via its associations with other proteins, including the sorting nexin SNX1. Mutations in this gene are associated with Parkinson's disease. [provided by RefSeq, Jun 2016]

DNAJC13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DNAJC13. . Gene score misZ 2.2836 (greater than the threshold 3.09). Trascript score misZ 3.3776 (greater than threshold 3.09). GenCC has associacion of gene with hereditary late onset Parkinson disease.

BP4

Computational evidence support a benign effect (MetaRNN=0.076388985).

BS2

High AC in GnomAd4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DNAJC13	NM_015268.4 linkuse as main transcript	c.289G>A	p.Ala97Thr	missense_variant	4/56	ENST00000260818.11	NP_056083.3
DNAJC13	NM_001329126.2 linkuse as main transcript	c.289G>A	p.Ala97Thr	missense_variant	4/57		NP_001316055.1
DNAJC13	XM_047447819.1 linkuse as main transcript	c.289G>A	p.Ala97Thr	missense_variant	4/57		XP_047303775.1
DNAJC13	XM_047447820.1 linkuse as main transcript	c.289G>A	p.Ala97Thr	missense_variant	4/56		XP_047303776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
DNAJC13	ENST00000260818.11 linkuse as main transcript	c.289G>A	p.Ala97Thr	missense_variant	4/56	1	NM_015268.4	ENSP00000260818	P1
DNAJC13	ENST00000486798.5 linkuse as main transcript	n.354G>A		non_coding_transcript_exon_variant	4/20	1
DNAJC13	ENST00000650455.1 linkuse as main transcript	c.289G>A	p.Ala97Thr	missense_variant, NMD_transcript_variant	4/57			ENSP00000496825

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000150

AC:

AN:

206156

Hom.:

AF XY:

0.000159

AC XY:

AN XY:

113068

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000314

Gnomad ASJ exome

AF:

0.00279

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000101

Gnomad OTH exome

AF:

0.000425

GnomAD4 exome

AF:

0.0000748

AC:

106

AN:

1417486

Hom.:

Cov.:

AF XY:

0.0000738

AC XY:

AN XY:

704778

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000281

Gnomad4 ASJ exome

AF:

0.00260

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000191

Gnomad4 OTH exome

AF:

0.000240

GnomAD4 genome

AF:

0.0000855

AC:

AN:

152054

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000299

Hom.:

Bravo

AF:

0.000125

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000107

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 22, 2022

The c.289G>A (p.A97T) alteration is located in exon 4 (coding exon 3) of the DNAJC13 gene. This alteration results from a G to A substitution at nucleotide position 289, causing the alanine (A) at amino acid position 97 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.044

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.026

MetaRNN

Benign

0.076

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.30

Sift

Benign

0.26

Sift4G

Benign

0.34

Polyphen

1.0

Vest4

0.57

MVP

0.37

MPC

0.44

ClinPred

0.25

GERP RS

5.9

Varity_R

0.27

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over